Susceptibility to many autoimmune diseases is linked to the immune response genes (IR genes), found either in the I region of the murine major histocompatibility comples (H-2) or in the HLA region of the human major histocompatibility complex. This relationship between disease susceptibility and IR genes has been exploited to develop a novel immunosuppressive therapy for models of autoimmune disease including acute and chronic relapsing experimental allergic encephalomyelitis (EAE), experimental autoimmune myasthenia gravis (EAMG), NZB/W F1 lupus-nephritis, experimental autoimmune thyroiditis, streptozocin induced diabetes mellitus, and collagen induced arthritis. In EAE anti I-A antibodies can reverse ongoing paralytic disease. The mechanism whereby anti I-A suppresses EAE will be studied using T cell clones reactive to myelin basic protein that induce EAE. In addition, the effect of anti I-A on the general cellular and humoral status of the recipient will be examined. Finally, the role of IR gene products in the antigen specific suppression of EAE with myelin basic protein-spleen cell conjugates will be examined.